Referenced in: none

Automatically associated channels: TRP , TRPM , TRPML , TRPML1

Title: The cation channel mucolipin-1 is a bifunctional protein that facilitates membrane remodeling via its serine lipase domain.

Authors: Janice M Laplante, John L Falardeau, Edward M Brown, Susan A Slaugenhaupt, Peter M Vassilev

Journal, date & volume: Exp. Cell Res., 2011 Apr 1 , 317, 691-705

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21256127

Abstract
Phospholipase modulators have been shown to affect the topology of lipid bilayers and the formation of tubulo-vesicular structures, but the specific endogenous phospholipases involved have yet to be identified. Here we show that TRPML1 (MLN1), a Ca(2+)-permeable channel, contributes to membrane remodeling through a serine lipase consensus domain, and thus represents a novel type of bifunctional protein. Remarkably, this serine lipase active site determines the ability of MLN1 to generate tubulo-vesicular extensions in mucolipin-1-expressing oocytes, human fibroblasts and model membrane vesicles. Our demonstration that MLN1 is involved in membrane remodeling and the formation of extensions suggests that it may play a role in the formation of cellular processes linked to the late endosome/lysosome (LE/L) pathway. MLN1 is absent or mutated in patients with mucolipidosis IV (MLIV), a lysosomal disorder with devastating neurological and other consequences. This study provides potential insight into the pathophysiology of MLIV.